Plasma 5α-Reduced Androgens in Men and Hirsute Women: Role of Adrenals and Gonads*

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Abstract
The contributions of the adrenal glands and gonads to the plasma content of the 5α-reduced androgens [androsterone, 3α-androstanediol (3α-diol), and 5α-dihydrotestosterone (DHT)] and two of their precursors (androstenedione and testosterone) were evaluated in men and women. Androsterone values were markedly reduced and 3α-diol values were moderately reduced (P < 0.003 and P < 0.03, respectively) in men with Addison's disease compared to normal men. Metyrapone administration to women produced supranormal concentrations of androsterone (P < 0.02), 3α-diol (P < 0.003), and androstenedione (P < 0.003), whereas DHT and testosterone values were not elevated significantly. Oral contraceptives administered for several weeks to six normal women resulted in subnormal plasma levels of androsterone (P < 0.004) and androstenedione (P < 0.04). All five androgens were elevated significantly in thirty premenopausal women with idiopathic hirsutism and reduced significantly (P < 0.05–0.001) by 3 weeks of therapy with oral dexamethasone (0.75 mg/day). Elevation of plasma 3α-diol was the most commonly observed abnormality (over 90%) in the hirsute women. The mean ratio between the adrenal and peripheral vein content of androstenedione was 32 (n = 6), and it was less than 6 for the other androgens. Direct adrenal cortical secretion accounts for a minor proportion of the plasma level of androsterone, 3a-diol, and DHT. Plasma androsterone is derived mainly from precursors from the adrenal cortices in both men and women. 3a-Diol and DHT appear to arise largely from testicular steroidal precursors in men and from both adrenal and ovarian precursors in normal and hirsute women.